tbuckley/cabot-search huggingface dataset:
Immunomodulatory effect of locoregional therapy in the tumor microenvironment
Authors: Lin Xie, Zhiqiang Meng
Journal: Molecular Therapy (2023)

Cancer immunotherapy appears to be a promising treatment option; however, only a subset of patients with cancer responds favorably to treatment. Locoregional therapy initiates a local antitumor immune response by disrupting immunosuppressive components, releasing immunostimulatory damage-associated molecular patterns, recruiting immune effectors, and remodeling the tumor microenvironment. Many studies have shown that locoregional therapy can produce specific antitumor immunity alone; nevertheless, the effect is relatively weak and transient. Furthermore, increasing research efforts have explored the potential synergy between locoregional therapy and immunotherapy to enhance the long-term systemic antitumor immune effect and improve survival. Therefore, further research is needed into the immunomodulatory effects of locoregional therapy and immunotherapy to augment antitumor effects. This review article summarizes the key components of the tumor microenvironment, discusses the immunomodulatory role of locoregional therapy in the tumor microenvironment, and emphasizes the therapeutic potential of locoregional therapy in combination with immune checkpoint inhibitors.
Telomerase inhibition is an effective therapeutic strategy in<i>TERT</i>promoter-mutant glioblastoma models with low tumor volume
Authors: Elisa Aquilanti, Lauren Kageler, Jacqueline Watson, Duncan M Baird, Rhiannon E Jones, Marie Hodges, Zsofia M Szegletes, John G Doench, Craig A Strathdee, Jose Ricardo Mc Faline Figueroa, Keith L Ligon, Matthew Beck, Patrick Y Wen, Matthew Meyerson
Journal: Neuro-Oncology (2023)

Glioblastoma is one of the most lethal forms of cancer, with 5-year survival rates of only 6%. Glioblastoma-targeted therapeutics have been challenging to develop due to significant inter- and intra-tumoral heterogeneity. Telomerase reverse transcriptase gene (TERT) promoter mutations are the most common known clonal oncogenic mutations in glioblastoma. Telomerase is therefore considered to be a promising therapeutic target against this tumor. However, an important limitation of this strategy is that cell death does not occur immediately after telomerase ablation, but rather after several cell divisions required to reach critically short telomeres. We, therefore, hypothesize that telomerase inhibition would only be effective in glioblastomas with low tumor burden.
Commercial Hair Analysis
Authors: Stephen Barrett
Journal: JAMA (1985)

Hair samples from two healthy teenagers were sent under assumed names to 13 commercial laboratories performing multimineral hair analysis. The reported levels of most minerals varied considerably between identical samples sent to the same laboratory and from laboratory to laboratory. The laboratories also disagreed about what was "normal" or "usual" for many of the minerals. Most reports contained computerized interpretations that were voluminous, bizarre, and potentially frightening to patients. Six laboratories recommended food supplements, but the types and amounts varied widely from report to report and from laboratory to laboratory. Literature from most of the laboratories suggested that their reports were useful in managing a wide variety of diseases and supposed nutrient imbalances. However, commercial use of hair analysis in this manner is unscientific, economically wasteful, and probably illegal. (<i>JAMA</i>1985;254:1041-1045)
The Health Care Quality Improvement Initiative
Authors: Stephen F. Jencks
Journal: JAMA (1992)

THIS ARTICLE describes how the Health Care Financing Administration (HCFA) is reshaping its approach to improving care for Medicare beneficiaries. The goal of the Health Care Quality Improvement Initiative (HCQII) is to move from dealing with individual clinical errors to helping providers to improve the mainstream of care. Such a reform implies profound changes. First, the processes and criteria for review change: instead of having clinicians use essentially intuitive local criteria to find problems in individual cases, peer review organizations (PROs) will use explicit, more nationally uniform criteria to For editorial comment see p 917. examine patterns of care and patterns of outcomes. Second, the immediate objective changes: PROs will focus primarily on persistent differences between the observed and the achievable in both care and outcomes and less on occasional, unusual deficiencies in care. Third, the ultimate method changes: PROs will help providers identify problems and their solutions by monitoring
Nimodipine After Resuscitation From Out-of-Hospital Ventricular Fibrillation
Authors: Risto O. Roine
Journal: JAMA (1990)

One hundred fifty-five consecutive patients resuscitated after out-of-hospital ventricular fibrillation by a physician-manned advanced life support unit were randomly assigned to receive nimodipine or placebo at a dosage of 10 μg/kg as an intravenous injection immediately after restoration of spontaneous circulation, followed by an infusion of 0.5 μg/kg per minute for 24 hours. No significant difference was found in the 1-year survival rate of nimodipine-treated (30 [40%] of 75 patients) and placebo-treated patients (29 [36%] of 80 patients). Recurrent ventricular fibrillation during the treatment occurred in one patient in the nimodipine group compared with 12 patients in the placebo group. In a post hoc analysis of patients with very long delays in advanced life support (more than 10 minutes), the 1-year survival rate was higher with nimodipine (eight [47%] of 17 patients) than with placebo (two [8%] of 26 patients). Nimodipine may be of benefit in patients with delayed resuscitation. (<i>JAMA</i>. 1990;264:3171-3177)
Automatic External Defibrillators Used by Emergency Medical Technicians
Authors: Richard O. Cummins
Journal: JAMA (1987)

In a randomized controlled clinical trial, the effectiveness of emergency medical technician (EMT) use of automatic external defibrillators (AEDs) was compared with EMT use of standard defibrillators for patients in cardiac arrest. A total of 321 cardiac arrest patients were treated during the study: 116 were treated by EMTs using the AED (AUTO group), 158 were treated by EMTs using the standard defibrillators (standard group), and 47 were treated by EMTs using the standard defibrillator when they were assigned to use the AED. There were no significant differences in hospital admission or discharge rates between the AUTO group (54% admitted, 28% discharged) and the standard group (52% admitted, 23% discharged) for patients in ventricular fibrillation (VF), for patients in non-VF rhythms, or for all patients combined. The only significant difference observed was in the time from power ON to first shock: 1.1 minutes average AUTO group and 2.0 minutes average standard group. The treatment groups did not differ significantly in sensitivity for VF (78%AED, 76% standard), specificity for non-VF rhythms (100% AED, 95% standard), or rates of defibrillation to a non-VF rhythm (62% AED, 57% standard). We conclude that in clinical outcomes and device performance, AEDs are comparable with standard defibrillators and should be considered an acceptable alternative. Automatic external defibrillators appear to have advantages over standard defibrillators in training, skill retention, and faster operation. Such devices can make early defibrillation available for a much larger portion of the population. They are a major innovation for the prehospital care of cardiac arrest patients. (<i>JAMA</i>1987;257:1605-1610)
Spark-Generating Properties of Electrode Gels Used During Defibrillation
Authors: Russell S. Hummel
Journal: JAMA (1988)

After a defibrillation attempt started a fire in an oxygen-enriched intensive care unit environment, seven popular electrode gels were tested for spark-generating properties by repeated 360-J electrical discharges into a 50-Ω test load. Gels with low initial impedance (7±1 Ω) allowed a high current flow (51 ±1 A), maintained a cool temperature (27°C to 33°C), and did not spark. Gels with high initial impedance (125 ±14 Ω) allowed less current (26 ±2 A), heated to 52°C±2°C, liquified, and generated an electrical spark after the fourth or fifth discharge. Federal standards should be developed to identify and label electrode gels that can be used safely for high-current applications such as defibrillation. (<i>JAMA</i>1988;260:3021-3024)
Atropine Poisoning in Children During the Persian Gulf Crisis
Authors: Yona Amitai
Journal: JAMA (1992)

<h3>Objective.</h3> —To evaluate the effects of high doses of atropine in children accidentally injected with automatic atropine injectors. These were distributed in Israel during the Persian Gulf Crisis as an antidote for chemical warfare agents. <h3>Design and Setting.</h3> —A national survey in pediatric emergency departments in Israel, involving 22 medical centers, with prospective data collection in 14 centers. <h3>Patients.</h3> —Children (n=268) presenting to emergency departments following misuse of automatic atropine injectors. <h3>Main Outcome Measures.</h3> —Documentation of atropine dose and clinical manifestations; determination of a clinical severity score and its correlation with atropine dose; measurements of serum atropine levels in six patients. <h3>Results.</h3> —Over a period of 4 months, 268 cases were reported, of which 240 were clinically evaluated. The most common site of injection (75%) was the finger or palm. Doses were up to 17-fold higher than standard doses for age. In 116 children (48%), systemic effects of atropine were observed, and 20 (8%) had severe atropinization. Seizures and life-threatening arrhythmias were not reported, and there were no fatalities. The severity of atropinization was correlated with the dose following a classic nonlinear, dose-response relationship. Serum atropine levels (6.2 to 61.0 ng/mL) were much higher than those observed after administration of therapeutic doses. <h3>Conclusions.</h3> —The high incidence of injection in the hand implies accidental use of automatic atropine injectors among children. The lack of mortality or life-threatening complications from injection of large doses of atropine attests to its relative safety in children. The low risk from atropine injections weighed against expected benefit as a lifesaving antidote justifies the distribution of personal atropine injectors to children at risk of organophosphorus nerve agent attack. (<i>JAMA</i>. 1992;268:630-632)
Chronic Fatigue in Primary Care
Authors: Kurt Kroenke
Journal: JAMA (1988)

Although fatigue is one of the most common complaints in ambulatory care, research has been minimal. Of the 1159 consecutive patients surveyed in two adult primary-care clinics, 276 (24%) indicated that fatigue was a major problem. Fatigue was more prevalent in women than in men (28% vs 19%). Extensive clinical, laboratory, psychometric, and functional data were gathered for 102 fatigued patients and 26 controls. Laboratory testing was not useful in detecting unsuspected medical conditions or in determining the cause of fatigue. Depression or somatic anxiety or both were suggested by screening psychometric instruments in 82 fatigued patients (80%) compared with three controls (12%). Global dysfunction was marked, as reported by patients on the Sickness Impact Profile. The mean score on the Sickness Impact Profile of 11.3 for fatigued patients is similar to that reported for patients with major medical illnesses. After one year of follow-up, only 29 fatigued patients (28%) had improved. The high prevalence, persistence, and functional consequences of fatigue mandate a search for effective therapy. (<i>JAMA</i>1988;260:929-934)
Marihuanann Psychosis
Authors: John A. Talbott
Journal: JAMA (1969)

A clinical syndrome of acute psychosis associated with<i>Cannabis</i>derivatives and environmental stress has been observed in 12 soldiers seen in Vietnam. Each case was characteristic of acute toxic psychosis with organic features and ten cases had paranoid features as well. Factors unique to Vietnam and combat situations seem pertinent; treatment was conservative and supportive.
Increasing Incidence of Tuberculosis in a Prison Inmate Population
Authors: M. Miles Braun
Journal: JAMA (1989)

The incidence of tuberculosis (TB) among inmates of the New York State prison system increased from 15.4 per 100 000 in 1976 through 1978 to 105.5 per 100 000 in 1986. Matching of TB and acquired immunodeficiency syndrome registries indicated that the majority (56%) of inmates with TB reported in 1985 and 1986 had acquired immunodeficiency syndrome or human immunodeficiency virus infection; none were known to be human immunodeficiency virus seronegative. A case-control study examined 59 inmates with TB reported from 1984 through 1986 and 59 matched control inmates without TB. Inmates who reported street drug use were more likely to develop TB: odds ratio, 9.7; 95% confidence interval, 2.8 to 33.6 and odds ratio, 7.3; 95% confidence interval, 0.9 to 59.3 by unconditional and conditional logistic regression analyses, respectively. Although the majority of cases are thought to be due to reactivation of latent infection, phage typing of 16<i>Mycobacterium tuberculosis</i>cultures suggested the possibility of inmate-to-inmate transmission in at least one cluster of three cases. It is of crucial importance that TB control measures be reinforced in the prison setting to counter the increased risk created by human immunodeficiency virus infection. (<i>JAMA</i>1989;261:393-397)
Incidence and Characteristics of Preventable latrogenic Cardiac Arrests
Authors: Susanna E. Bedell
Journal: JAMA (1991)

We studied the contribution of iatrogenic illness to cardiac arrest among patients hospitalized in 1981 in a university teaching hospital. During this 1-year period, 28 (14%) of 203 arrests in which resuscitation was attempted followed an iatrogenic complication. Seventeen (61%) of the 28 patients died. The demographic characteristics of patients with iatrogenic arrest did not differ strikingly from those of other patients who arrested. However, patients with iatrogenic arrest were less likely to be in cardiogenic shock or to have suffered an acute myocardial infarction prior to arrest. They were more likely to survive to discharge from the hospital and to be taking digoxin or antiarrhythmic medication prior to arrest. Among the 28 cases of iatrogenic cardiac arrest, 18 (9% of all arrests) might have been prevented by stricter attention to the patient's history, findings on physical examination, and laboratory data. The most common causes of potentially preventable arrest were medication errors and toxic effects (44%) as well as suboptimal response by physicians to clinical signs and symptoms (28%), most frequently dyspnea and tachypnea. Rapid, appropriate response to abnormal drug levels, to electrocardiographic signs of adverse drug effects, and to signs and symptoms of congestive heart failure or toxic effects from digoxin might decrease the incidence of cardiac arrest among hospitalized patients. (<i>JAMA</i>. 1991;265:2815-2820)
Male Gonadal Dysfunction in Hodgkin's Disease
Authors: Ramona M. Chapman
Journal: JAMA (1981)

Forty-seven men (median age, 31.5 years) were studied prospectively to assess the effect of Hodgkin's disease and subsequent chemotherapy on gonadal function. Before therapy, 16 (43%) of 37 men were functionally subfertile, as assessed by impotence (four of 37) and "inadequate" sperm counts (12 of 37). Histological abnormalities were noted in eight of nine pretreatment testicular biopsy specimens. Additionally, changes were noted in blood hormone levels and libido. After completion of only two cycles of chemotherapy, 14 of 14 men became persistently azoospermic, with blood follicle-stimulating hormone levels four to five times normal. Posttreatment testicular biopsy specimens confirmed germ cell aplasia. During therapy 17 (81%) of 21 men had mild or no libido; irritability in 16 (84%) of 19 and violence in four (18%) of 22 caused additional family distress. While it is clear that cytotoxic therapy induces infertility, these data further indicate that a proportion of men have gonadal dysfunction prior to treatment. (<i>JAMA</i>1981;245:1323-1328)
Whatever Happened to the Health Insurance Crisis in the United States?
Authors: Karen Donelan
Journal: JAMA (1996)

FOUR YEARS AGO, in the presidential campaign, in major medical journals and medical associations, in the media, and in civic groups, our nation was engaged in a great debate about the best way to provide health insurance coverage to all Americans. By contrast, these debates have been conspicuous by their absence in this election year. The health system reform debate was marked by some controversy about whether there was a health insurance crisis at all.<sup>1</sup>On one side were those who said that most of the uninsured could get care when they needed it, a view that was expressed in a commentary in the<i>Wall Street Journal</i>in 1994 that noted that "these [uninsured] citizens are not denied health care" and only 1 in 5 uninsured (about 3% of the population) cannot obtain affordable insurance.<sup>2</sup>On the other side were those who claimed that many of the uninsured
Defensive Medicine and Obstetrics
Authors: Laura-Mae Baldwin
Journal: JAMA (1995)

<h3>Objective.</h3> —To test the hypothesis that physicians with greater malpractice claims exposure, either through personal experience or in their practice environment, will use more prenatal resources and have a higher cesarean delivery rate than physicians with lesser claims exposure. <h3>Design.</h3> —Retrospective cohort study using county malpractice defendant rate data from the Washington State Physicians Insurance and Exchange Association and prenatal care, delivery method, and self-reported obstetric suit experience data from the Content of Obstetrical Care Study database. <h3>Setting.</h3> —Washington State obstetric practices. <h3>Participants.</h3> —Stratified random samples of obstetrician-gynecologists and family physicians. <h3>Main Outcome Measures.</h3> —The rates of obstetric ultrasound use, referral and consultation, prenatal care resource use, and cesarean delivery. <h3>Results.</h3> —After controlling for patient, physician, and sociodemographic characteristics, we found no difference in prenatal resource use or cesarean delivery rate for low-risk patients between physicians with more and less exposure to malpractice claims. <h3>Conclusions.</h3> —This study does not support an association between the malpractice experience or exposure of individual physicians and an increase in the use of prenatal resources or cesarean deliveries for the care of low-risk obstetric patients. (<i>JAMA</i>. 1995;274:1606-1610)
Chromosome‐level genomic assembly and allergome inference reveal novel allergens in <i>Tyrophagus putrescentiae</i>
Authors: Ying Zhou, Pavel B. Klimov, Xiaohong Gu, Zhiwei Yu, Xiaochuan Cui, Qingqing Li, Ruilin Pan, Cunyin Yuan, Fangfang Cai, Yubao Cui
Journal: Allergy (2023)

Figure S1 Figure S2 Table S1–S7 Data S1 Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Significantly lower infection fatality rates associated with SARS-CoV-2 Omicron (B.1.1.529) infection in children and young people: Active, prospective national surveillance, January-March 2022, England
Authors: Erjola Hani, Marta Bertran, Annabel Powell, Hannah Williams, Paul Birrell, Daniela DeAngelis, Mary E Ramsay, Godwin Oligbu, Shamez N Ladhani
Journal: Journal of Infection (2023)
Tobacco Dependence and the Nicotine Patch
Authors: Michael C. Fiore
Journal: JAMA (1992)

<h3>Objective.</h3> —A comprehensive review of transdermal nicotine treatment for tobacco dependence, with recommendations derived from the research literature. <h3>Data Sources.</h3> —English-language clinical trials. <h3>Study Selection.</h3> —Clinical trials using placebo-controlled, double-blind methodology (11 studies) with at least 6 months of follow-up after treatment (eight studies) and biochemical verification of smoking status. <h3>Data Synthesis.</h3> —Nicotine patches produce end-of-treatment smoking cessation rates that range from 18% to 77%; these rates are about twice those of placebo-treated subjects. Nicotine patches produced 6-month abstinence rates of 22% to 42%, while placebo patches produced quit rates of 5% to 28%. Nicotine patches appear to reduce some, but not all, nicotine withdrawal symptoms. For instance, while the patch reduces craving for cigarettes and negative moods, it does not appear to reduce hunger or weight gain. The clinical trials literature suggests that proper adjuvant smoking cessation counseling is crucial in determining successful long-term outcome with the nicotine patch, and suggests that 6 to 8 weeks of patch therapy may be an adequate duration for most patients. <h3>Conclusions.</h3> —Nicotine patches are an effective aid to tobacco dependence treatment. However, success rates vary greatly across research studies and may be influenced highly by the nature and intensity of adjuvant smoking cessation counseling. More research is needed to identify optimal duration, dosage, and individualization of patch therapy. The impact of nicotine patches (more than 5 million users with $1 billion in sales for 1992) also raises important ethical and public health issues. (<i>JAMA</i>. 1992;268:2687-2694)
Re: Giuseppe Basile, Marco Bandini, Ewan A. Gibb, et al. Neoadjuvant Pembrolizumab and Radical Cystectomy in Patients with Muscle-invasive Urothelial Bladder Cancer: 3-Year Median Follow-up Update of PURE-01 Trial. Clin Cancer Res 2022;28:5107–14
Authors: Chao Quan, Jinbo Chen, Jiao Hu
Journal: European Urology (2023)
Reply to Jon Griffin. TIME for a Change? Multimarker Assessment of the Tumour Immune Microenvironment and Metastatic Site Biopsy to Improve Immunotherapy Response Prediction in Muscle-invasive Bladder Cancer. Eur Urol. 2023;43:143–4
Authors: Niklas Klümper, Michael Hölzel, Markus Eckstein
Journal: European Urology (2023)
Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes
Authors: Julia Flammer, Tradite Neziraj, Stephan Rüegg, Anne-Katrin Pröbstel
Journal: Drugs (2023)

Seizures and epilepsy can result from various aetiologies, yet the underlying cause of several epileptic syndromes remains unclear. In that regard, autoimmune-mediated pathophysiological mechanisms have been gaining attention in the past years and were included as one of the six aetiologies of seizures in the most recent classification of the International League Against Epilepsy. The increasing number of anti-neuronal antibodies identified in patients with encephalitic disorders has contributed to the establishment of an immune-mediated pathophysiology in many cases of unclear aetiology of epileptic syndromes. Yet only a small number of patients with autoimmune encephalitis develop epilepsy in the proper sense where the brain transforms into a state where it will acquire the enduring propensity to produce seizures if it is not hindered by interventions. Hence, the term autoimmune epilepsy is often wrongfully used in the context of autoimmune encephalitis since most of the seizures are acute encephalitis-associated and will abate as soon as the encephalitis is in remission. Given the overlapping clinical presentation of immune-mediated seizures originating from different aetiologies, a clear distinction among the aetiological entities is crucial when it comes to discussing pathophysiological mechanisms, therapeutic options, and long-term prognosis of patients. Moreover, a rapid and accurate identification of patients with immune-mediated epilepsy syndromes is required to ensure an early targeted treatment and, thereby, improve clinical outcome. In this article, we review our current understanding of pathogenesis and critically discuss current and potential novel treatment options for seizures and epilepsy syndromes of underlying or suspected immune-mediated origin. We further outline the challenges in proper terminology.